Determinants of Cardiovascular Disease Risk Factors Among Youth With Type 1 Diabetes (CARDEA)

Early Myocardial Morphologic and Functional Changes and Their Association With Diet and Physical Activity in Adolescents With Type 1 Diabetes

Type 1 diabetes mellitus (T1D) is the most common form of diabetes among children and youth, and it is increasing around the world, particularly among children under 5 years. This is worrisome given the chronic nature of the disease and its strong association with an increased risk of cardiovascular disease (CVD). Evidence suggests that markers of CVD are already present in children with T1D, making prevention a clinical and public health priority in this high-risk population. Despite this, a good understanding of what factors predispose children with T1D to CVD is still lacking.

Our study aims to better understand in this population what individual, familial and environmental characteristics increase the risk for heart disease, how to best measure it early on and what are the potential mechanisms underlying the heightened risk for heart disease in youth with T1D. Specifically, we aim to:

1. compare established risk factors (dyslipidemia, hypertension) with novel early markers for CVD (cardiac phenotype, arterial stiffness, endothelial function) in adolescents with T1D and healthy controls;
2. examine the associations between these novel early markers with: i) lifestyle habits; ii) measures of inflammation; and iii) markers of oxidative stress among adolescents with T1D and healthy controls, and determine group differences in these associations;
3. explore, across both groups, the associations between these established and novel early markers of CVD with neighborhood features.
4. Determine sex and gender differences in novel markers of CVD (cardiac structure/myocardial oxygenation, vascular studies including endothelial function and arterial stiffness) in youth with T1D and healthy controls;
5. Determine, across both groups, sex and gender differences in associations between markers of CVD and lifestyle habits, specifically: i) moderate-to-vigorous physical activity (MVPA); ii) dietary intake (carbohydrates, sugar, saturated/trans-fat, fiber, food groups); iii) sedentary behavior; and iv) sleep;
6. Measure changes in novel markers of CVD from adolescence to early adulthood among individuals with T1D and healthy controls;
7. Assess whether lifestyle habits in adolescence are prospectively associated with established (dyslipidemia, hypertension) and novel (cardiac structure/myocardial oxygenation, endothelial function, arterial stiffness) markers of CVD in early adulthood, and if these associations differ according to T1D status, adiposity, sex and gender.

To achieve these objectives, we will compare 300 participants aged 14-18 years with T1D to 300 healthy controls. 100 participants from each group will be reassessed at the age of 22-26 yo. Lifestyle habits include assessments of physical activity, sleep, sedentary behavior, fitness and dietary intake. Blood pressure and lipid profiles will be measured. Cardiac structure/function will be evaluated by non-contrast cardiac magnetic resonance imaging (CMR). Aortic distensibility will be determined by pulse wave velocity. Endothelial function will be determined by flow-mediated dilation. Inflammatory markers and endogenous antioxidants will be measured in blood. Intestinal microbiota will be assessed. Neighbourhood features include built and social environment indicators and air quality.

Our study provides an exceptional opportunity to increase our knowledge on what factors predispose children with T1D to cardiovascular disease. Understanding the interplay between T1D, lifestyle habits and metabolic markers and CVD is critical to developing effective prevention strategies for these vulnerable children.

Study Overview

• Status: Suspended
• Conditions: Type 1 Diabetes; Cardiovascular Risk Factor

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

T1D group: Sainte-Justine Hospital's Diabetes Clinic patients

Control group: Community sample

Description

Inclusion Criteria:

• Diagnosis of T1D (for the T1D group) or no diagnosis of any type of diabetes (for the control group)
• 14 to 18 years old

Exclusion Criteria:

• Youth with another type of diabetes such as T2D
• Conditions that could limit their ability to participate in the study
• Known pathology that would influence their risk for CVD
• Siblings of a participant already enrolled in the study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Diabetics; Girls and boys living with Type 1 Diabetes.
Control; Age and sex matched participants without any type of diabetes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cardiac structure (MRI)	Baseline measurement
Endothelial function (Flow-mediated dilation)	Baseline measurement
Vascular structure (Pulse-wave velocity)	Baseline measurement

Secondary Outcome Measures

Outcome Measure	Time Frame
Dyslipidemia	Baseline measurement
Hypertension	Baseline measurement

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Investigators: Principal Investigator: Mélanie Henderson, MD, Ph.D, St. Justine's Hospital

Publications and helpful links

General Publications

• Henderson M, Friedrich M, Van Hulst A, Pelletier C, Barnett TA, Benedetti A, Bigras JL, Drapeau V, Lavoie JC, Levy E, Mathieu ME, Nuyt AM. CARDEA study protocol: investigating early markers of cardiovascular disease and their association with lifestyle habits, inflammation and oxidative stress in adolescence using a cross-sectional comparison of adolescents with type 1 diabetes and healthy controls. BMJ Open. 2021 Sep 8;11(9):e046585. doi: 10.1136/bmjopen-2020-046585.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2017
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: March 9, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 28, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Adolescents; Cardiovascular disease; Sleep; Physical activity; Diet; Type 1 Diabetes; Cardiac MRI; Sedentary behavior
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2016-936; 366194 (Other Grant/Funding Number: Canadian Institutes of Health Research); G-16-00012590 (Other Grant/Funding Number: Heart and Stroke Foundation of Canada)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No